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Cryo-EM and the newest techniques in image acquisition are having a major impact on our ability to determine the biomolecular structure. But the challenges in controlling and stabilising living cells means there’s much that can be learned from techniques used to observe more stable media in materials science. The Ernst Ruska-Centre seeks to take the lessons of materials science and apply it to its state-of-the-art expertise in biomolecular Cryo-EM. Founded in 2004, the Ernst Ruska-Centre (ER-C) is based at the Forschungszentrum Jülich and houses some of the world's most advanced electron microscopes and tools for nanocharacterisation. The scientific research combines current issues in condensed matter physics and cryo-EM on biomacromolecules with the aim of advancing electron microscopy methods. The Ernst Ruska Centre has a long-standing tradition of high-end electron microscopy in material sciences, but has only recently expanded its portfolio to cryo-electron microscopy infrastructure for the investigation of biological specimens. Employing state of the art computing and data handling, the centre is able to conduct single particle analysis and discover the structure of isolated proteins. The centres expertise in Cryo-EM for biological samples, as well as in many other means they are building and expanding into a user centre in which they merge the methods of physical and biological sciences. One innovative approach that the centre is applying to Cryo-EM is Scanning Transmission Electron Microscopy (STEM), an approach that’s common in physical sciences but rare in biology. The team is applying this to probe the tobacco mosaic virus (TMV) at unprecedented scales. Their approach uses the integrated differential phase contrast mode also known as iDPC–STEM, enabling a cryo-EM structure determination for TMV at 3.5 Å resolution using single-particle reconstruction methods. This demonstrates that STEM imaging can be applied to vitrified single-particle specimens to determine near-atomic resolution cryo-EM structures of biological macromolecules. Beyond this proof of concept, the ER-C is already using its expertise to investigate more specific biomolecular processes. One recently published research project looks at membrane remodeling and re-shaping by the phage shock protein (Psp) system. Cryo-EM was used to visualise how the main Psp effector, PspA, remodels membrane vesicles into μm-sized structures, as well as linking previously separate lipid structures. One of many key findings was that PspA matches the structural organization of ESCRT-III proteins, where this remodelling mechanism has more commonly been seen. There’s much more to be discovered using Cryo-EM and research is ongoing into game-changing new methodologies at the Ernst Ruska-Centre. The unique interaction between biological and physical disciplines means expertise from both fields is naturally transferred to cross exciting new horizons in single molecular imaging. A new centre is currently under construction which will drastically improve the capacity and scope of the work the ER-C is doing and further change the game in structural biology.